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Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery
Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa
Division of Neurosciences, Department of Neurology, University of the Witwatersrand, Johannesburg, 2193, South Africa
Division of Neurosciences, Department of Neurosurgery, University of Witwatersrand, Johannesburg, 2193, South Africa
Department of Medicinal Chemistry, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
* Author to whom correspondence should be addressed.
Received: 27 July 2011; Accepted: 4 August 2011 / Published: 23 September 2011
Abstract: Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8–43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery.
Keywords: nanotechnology; nanoparticles; nanocapsules; methacrylate copolymer; chitosan; oral drug delivery; bioavailability; crosslinking; molecular mechanics simulations
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Ngwuluka, N.C.; Pillay, V.; Choonara, Y.E.; Modi, G.; Naidoo, D.; Toit, L.C.; Kumar, P.; Ndesendo, V.M.; Khan, R.A. Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery. Int. J. Mol. Sci. 2011, 12, 6194-6225.
Ngwuluka NC, Pillay V, Choonara YE, Modi G, Naidoo D, Toit LC, Kumar P, Ndesendo VM, Khan RA. Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery. International Journal of Molecular Sciences. 2011; 12(9):6194-6225.
Ngwuluka, Ndidi C.; Pillay, Viness; Choonara, Yahya E.; Modi, Girish; Naidoo, Dinesh; Toit, Lisa C. du; Kumar, Pradeep; Ndesendo, Valence M.K.; Khan, Riaz A. 2011. "Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery." Int. J. Mol. Sci. 12, no. 9: 6194-6225.